POZ December 2012

POZ is the nation’s leading magazine about HIV/AIDS. Serving the community of people living with and those affected by HIV/AIDS since 1994.

Most likely it won’t be a single person—or a single research
team or institution—to discover the cure for HIV. Just like it
was with AIDS treatment research, it will be a massive
endeavor requiring monumental collaborative work between
test tube and animal scientists, the biotech and pharmaceutical industries, government and nongovernmental organizations, clinical trial experts and, of course, study volunteers.
In addition to the Seekers on the previous pages, the 27
researchers below further exemplify the scientific leadership
chipping away at the mystery of HIV persistence, many of
whom are also testing novel ways to achieve either eradication
or functional cures in the greatest number of people with HIV.
Much of their work wouldn’t be possible without significant funding from sources such as the Martin Delaney Collaboratory at the National Institutes of Health; amfAR, The
Foundation for AIDS Research; and the California Institute
for Regenerative Medicine.
Joseph Alvarnas and Richard Ambinder The City of Hope National
Medical Center and Johns Hopkins University researchers are enrolling
HIV-positive cancer patients into a transplant study that will involve
donors with the CCR5-Delta32 mutation that confers resistance to HIV.
They’re looking to duplicate the results of Timothy Brown’s case.
David Baltimore A 1975 Nobel Prize recipient currently at the California
Institute of Technology, Baltimore is exploring why existing ARVs don’t
clear HIV reservoirs—a step in figuring out what will work.
Paul Cameron The Melbourne-based Monash University scientist is
focusing on tissue-based dendritic cells, which can become infected
with HIV but don’t produce new virus. Figuring out what sets these cells
apart from others can potentially be applied to curative approaches.
Paula Cannon Using zinc finger nucleases (ZFNs) to genetically alter
CD4 cells is proving safe and effective in treatment studies. Laboratory
work conducted by Cannon of the University of Southern California
suggests it might be possible to do the same thing with stem cells to
rebuild entire immune systems resistant to HIV, thus curing the virus.
There are no studies in humans yet.
Julian Elliott Working with “Seeker” Steven Deeks, Monash University’s
Elliott is testing the alcohol dependency drug Antabuse (disulfiram)
as a way to flush HIV from its reservoirs. Like vorinostat (see “Seeker”
David Margolis), disulfiram inhibits HDAC, a class of enzymes that keep
HIV locked inside cells.
Koh Fujinaga While some researchers find ways to tease out HIV
from its hiding spots in reservoirs, Fujinaga of the University of
California at San Francisco has set out to understand what, exactly,
happens inside cells that end up sequestering HIV in the first place.
42 POZ DECEMBER 2012 poz.com
Hiroyu Hatano Might a common blood pressure medication—an ACE
inhibitor—successfully reduce fibrous tissue in lymph nodes, thereby
allowing a more effective immune response against HIV, particularly
in its hiding places? Hatano and her colleagues at the University of
California at San Francisco are currently exploring this theory.
Frederick Hecht and Daniel Douek Hecht of the University of California
at San Francisco is working with Douek of the NIH (along with “Seeker”
Sarah Palmer) to test their theory that ARV-unaffected immune system cells can make copies of themselves and the virus they contain, thus
creating HIV reservoirs. Figuring out which cells are involved, and how,
will allow researchers to design ways to clear the reservoirs and cure HIV.
Timothy Henrich Was Timothy Brown cured of his HIV because of the
chemotherapy, anti-CD4 cell antibody infusions, high-dose radiation or
the HIV-resistant stem cells he received? It could have been one therapy
or a combination of approaches. In working to figure out the answer,
Henrich of Brigham and Women’s Hospital in Boston is helping drive
new research. He also is investigating two more possible cure cases
following bone marrow transplants.
Keith Jerome and Hans-Peter Kiem Both of the Fred Hutchinson Cancer
Research Center in Seattle, Jerome and Kiem are developing proteins
known as endonucleases to target HIV. They’re also collaborating with
Sangamo BioSciences to further study the use of gene therapies to
render the immune system resistant to the virus.
Mathias Lichterfeld The Massachusetts General Hospital researcher
will explore whether a newly discovered group of CD4 cells, dubbed
T-memory stem cells, are a main site of HIV reservoirs that re-emerge
after ARV therapy is stopped. His group will look at drugs to purge virus
from these cells.
Robert Murphy The Northwestern University researcher heads the
ERAMUNE-2 study (see the sister clinical trial by “Seeker” Christine
Katlama), which intensifies HIV treatment to target actively
replicating cells and then uses an Ad5 HIV vaccine, an immune-based
therapy, to simultaneously attack the viral reservoirs. Preliminary
results from both studies are expected soon.
Douglas Nixon Did you know that several ancient viruses, called
HERVs, are embedded in our DNA and can become reactivated? By
exploring the antibodies our immune systems produce to control
these viruses, Nixon of the University of California at San Francisco
is hoping to develop a vaccine that can produce antibodies against
another DNA passenger: HIV.
Deborah Persaud and Katherine Luzuriaga The Johns Hopkins and
University of Massachusetts researchers, respectively, have been
studying a handful of adolescents who contracted HIV at birth yet have
no detectable virus and are antibody negative after spending their
childhoods on ARVs. How do their viral reservoirs and immune systems
differ compared with people who became HIV positive as adults?
They’re looking to find out.